Compositions and methods for inhibiting hedgehog pathway

Abstract

The present invention relates to the use of compositions and methods for treating or preventing a cancer condition in a subject. The use of composition comprises methods of treating or preventing cancer with agents that inhibit Hedgehog pathway activity. The pharmaceutical composition will further comprise agents that inhibit Smoothened receptor and/or Gli transcription in a subject.

1 . A method for treating or preventing cancer in a subject, comprising administering to the subject a pharmaceutical composition comprising an effective amount of at least one agent that inhibits at least one of Smoothened receptor, or Gli transcriptional activity, wherein
 Gli is highly expressed, and an agent is a small molecule represented by a compound having the chemical structure of:   
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         2 . The composition of  claim 1 , wherein said agent comprises a targeting moiety capable of binding to the surface of a cancer cell, wherein said targeting moiety is selected from the group consisting of aptamers, peptides, biodegradable materials, antibody-derived epitope binding domains, cellular ligands, and combination thereof. 
     
     
         3 . The method of  claim 1 , wherein the method further comprises: 
       determining Gli expression or Gli transcription activity of the said subject. 
     
     
         4 . The composition of  claim 1 , wherein at least one agent inhibits cancer cell or cancer stem cell growth. 
     
     
         5 . The composition of  claim 1 , wherein at least one agent is administered in nanoparticles containing an imaging agent with or without a targeting agent. 
     
     
         6 . The composition of  claim 1 , wherein at least one agent is administered to the subject in combination with one or more chemotherapeutic drugs, immunotherapy or radiation for treatment or prevention of cancer. 
     
     
         7 . The composition as claimed in  claim 1 , wherein said agent can be modified by at least one functional group which includes hydroxyl, methyl, carbonyl, carboxyl, amino, nitro, ether, phosphate, sulhydryl, fluromethyl, ester and carbonyl group. 
     
     
         8 . The composition of  claim 7 , wherein said agent comprises a targeting moiety capable of binding to the surface of a cancer cell, wherein said targeting moiety is selected from the group consisting of aptamers, peptides, biodegradable materials, antibody-derived epitope binding domains, cellular ligands, and combination thereof. 
     
     
         9 . The method of  claim 7 , wherein the method further comprises: 
       determining Gli expression or Gli transcription activity of the said subject. 
     
     
         10 . The composition of  claim 7 , wherein at least one agent inhibits cancer cell or cancer stem cell growth. 
     
     
         11 . The composition of  claim 7 , wherein at least one agent is administered in nanoparticles containing an imaging agent with or without a targeting agent. 
     
     
         12 . The composition of  claim 7 , wherein at least one agent is administered to the subject in combination with one or more chemotherapeutic drugs, immunotherapy or radiation for treatment or prevention of cancer.